Identifying tick genes could halt disease, bioterrorism threat

WEST LAFAYETTE, Ind. - Ticks as small as a freckle can transmit a number of illnesses for which there is no vaccine and, in some cases, no cure. These creatures even could become bioterrorism weapons.

To find new ways to control the tiny animals and halt the spread of the pathogens they carry, Purdue University researchers and colleagues from the University of Connecticut Health Center, the University of Notre Dame and Massachusetts Institute of Technology are undertaking the job of unraveling the genetic makeup of one variety of the creature, called the deer or black-legged tick.

"This will be the first time researchers have explored a tick genome in depth," said Purdue's Catherine Hill, project co-principal investigator. "It's crucial to learn how ticks spread serious illnesses because of the global health threats these diseases pose.

"From a bioterrorism standpoint, it's pretty clear ticks could transmit a number of diseases that intentionally could be introduced and conveyed to people."

The scientists involved in this project have formed the International Ixodes scapularis Sequencing Committee. One of the potential outcomes of this project may be development of vaccines to block transmission of microbes that cause tick-borne illnesses, said Hill, who spearheaded efforts to gain National Institutes of Health backing for the initial stages of the tick genome venture.

Hill and her Purdue researchers are preparing materials that will be the foundation of the sequencing project, she said. She already has begun extracting RNA from ticks at different stages of their lifecycle and from different tissues in the tick. These samples will provide the scientists with the first clues as to the types of genes present in ticks and how gene expression changes when ticks are infected with disease-causing microorganisms.

"Once we begin to collect the genome data, we will analyze what the genes do and how they control tick behavior, including how they are able to spread disease," she said.

Stephen Wikel is co-principal investigator on the project, which is funded by the NIH's National Institute of Allergy and Infectious Diseases.

"The tick genome project will extend our search for molecules that are essential for ticks to feed and transmit pathogens," said Wikel, director of the Center for Microbial Pathogenesis at the University of Connecticut Health Center.

The collaborators will delve into how ticks find animals to feed on, feeding methods, blood meal digestion, development of disease-causing microbes within the tick, tick reproduction, transmission of infectious agents, new control methods and evolutionary biology.

Bruce Birren and his team at The Broad Institute at MIT will do the initial sequencing of the deer tick genome. The sequence data will be used to identify tick genes. When this step is complete, the multi-institutional research team and other scientists throughout the world will use the genome data to search for ways to halt tick-borne illnesses.

An invertebrate creature known as an arthropod, ticks transmit, or vector, more pathogens to humans and other animals than any other blood-feeding organism. Indeed, experts now believe one tick type in the United States transmits West Nile virus, previously believed to be only mosquito-borne in this country.

Hill and her colleagues selected the deer tick, scientifically known as Ixodes scapularis, in part because of its large impact on human and animal health.

Deer ticks are the main vectors for Lyme disease, which is the most commonly reported tick-transmitted human disease in the United States. Lyme disease can cause lethargy, joint swelling and facial paralysis. Some of the symptoms can become chronic arthritis and neurological syndromes. In 2002 the Centers for Disease Control and Prevention recorded approximately 24,000 cases of the often-misdiagnosed and under-diagnosed illness. This was a 40 percent increase over the previous year.

A number of ticks in the United States spread pathogens that the CDC considers potential bioterrorism weapons. The family to which I. scapularis belongs, Ixodidae, carries many of the microbes included on the CDC's Select Biological Agents and Toxins list. Among the diseases caused worldwide by these organisms are Rocky Mountain spotted fever, tularemia, Crimean-Congo hemorrhagic fever and tick-borne encephalitic diseases.

Ticks spread disease by taking blood from an infected animal and then feasting on another animal. They need the blood to grow from egg to adult, and the adult female needs the blood to nourish her eggs.

In the case of Lyme disease-carrying deer ticks, the larvae feed on infected white-footed mice and other small mammals that harbor the pathogens. The tick develops into a nymph, which carries the Lyme disease-producing bacteria to people, pets and other animal species.

The tick's olfactory system, or what we call our noses, is in its feet. These organs recognize carbon dioxide, which animals, including people, emit when they exhale. Ticks lie in wait until they receive the carbon dioxide signal that a meal is nearby. Then they leap, sink their mouths into flesh, and gorge themselves while at the same time spreading insidious diseases.

Ticks feed on a diverse group of hosts including people, pets, livestock, reptiles and birds. Most of these are susceptible to the pathogens carried by one type of tick or another. Ticks have unique ways of interacting with both host and the disease-causing microbes they carry, Hill said. A host is the animal from which the tick sucks blood.

"Ticks stay on their host for a long time, and they've developed a complicated mechanism to avoid being detected," said Hill, an entomology assistant professor. "Ticks can increase the blood supply to the area where they're feeding. They release pain inhibitors so the host can't tell that they are present and a whole host of complicated proteins that prevent the host immune response from getting rid of them."

Currently very little is known about the tick genome, which is about two-thirds the size of the human genome, Hill said. Many animals and plants have similar genes with similar functions, but ticks have some unique genes different even from other invertebrates.

With a better understanding of the deer tick, researchers hope to learn much about the whole branch of the evolutionary tree that includes this arthropod, she said.

"This is an exciting opportunity to study this unique organism in a new way," Hill said. "We will be able to identify targets for development of novel insecticides to control ticks and new vaccines to control the pathogens they carry."

Other members of the team are Frank Collins, University of Notre Dame biology professor, and Vishvanath Nene, of TIGR - The Institute for Genomic Research - in Rockville, Md.